HTLV-1 tax specific [CD8.sup.+] T cells express low levels of Tim-3 in HTLV-1 infection: implications for progression to neurological complications

The T cell immunoglobulin mucin 3 (Tim-3) receptor is highly expressed on HIV-1-specific T cells, rendering them partially "exhausted" and unable to contribute to the effective immune mediated control of viral replication. To elucidate novel mechanisms contributing to the HTLV-1 neurologic...

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Published inPLoS neglected tropical diseases Vol. 5; no. 4
Main Authors Ndhlovu, Lishomwa C, Leal, Fabio E, Hasenkrug, Aaron M, Jha, Aashish R, Carvalho, Karina I, Eccles-James, Ijeoma G, Bruno, Fernanda R, Vieira, Raphaella G.S, York, Vanessa A, Chew, Glen M, Jones, R. Brad, Tanaka, Yuetsu, Neto, Walter K, Sanabani, Sabri S, Ostrowski, Mario A, Segurado, Aluisio C, Nixon, Douglas F, Kallas, Esper G
Format Journal Article
LanguageEnglish
Published Public Library of Science 01.04.2011
Subjects
Complications and side effects
Development and progression
Diagnosis
Health aspects
Histocompatibility antigens
HLA histocompatibility antigens
HTLV infections
Nervous system diseases
Physiological aspects
Risk factors
T cells
Brazil
United States
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Summary:The T cell immunoglobulin mucin 3 (Tim-3) receptor is highly expressed on HIV-1-specific T cells, rendering them partially "exhausted" and unable to contribute to the effective immune mediated control of viral replication. To elucidate novel mechanisms contributing to the HTLV-1 neurological complex and its classic neurological presentation called HAM/TSP (HTLV-1 associated myelopathy/tropical spastic paraparesis), we investigated the expression of the Tim-3 receptor on [CD8.sup.+] T cells from a cohort of HTLV-1 seropositive asymptomatic and symptomatic patients. Patients diagnosed with HAM/TSP down-regulated Tim-3 expression on both [CD8.sup.+] and [CD4.sup.+] T cells compared to asymptomatic patients and HTLV- 1 seronegative controls. HTLV-1 Tax-specific, HLA-A*02 restricted [CD8.sup.+] T cells among HAM/TSP individuals expressed markedly lower levels of Tim-3. We observed Tax expressing cells in both [Tim-3.sup.+] and [Tim-3.sup.-] fractions. Taken together, these data indicate that there is a systematic downregulation of Tim-3 levels on T cells in HTLV-1 infection, sustaining a profoundly highly active population of potentially pathogenic T cells that may allow for the development of HTLV-1 complications.
ISSN:1935-2727
1935-2735
DOI:10.1371/journal.pntd.0001030